Benjamin Wilfond

• University of Washington

A growing literature has explored the ethical obligations and current practices related to sharing aggregate results with research participants. However, no prior work has examined these issues in the context of pragmatic clinical trials. Several characteristics of pragmatic clinical trials may complicate both the ethics and the logistics of sharin...

Background Ethical responsibilities for monitoring and responding to signals of behavioral and mental health risk (such as suicidal ideation, opioid use disorder, or depression) in general clinical research have been described; however, pragmatic clinical trials (PCTs) raise new contextual challenges. Methods We use our experience with the PRISM (...

Background and objectives: Successful clinical integration of genomic sequencing (GS) requires evidence of its utility. While GS potentially has benefits (utilities) or harms (disutilities) across multiple domains of life for both patients and their families, there is as yet no empirically informed conceptual model of these effects. Our objective...

Genetic and genomic testing is reaching more people than ever, yet disparities in access to and application of hereditary cancer screening remain. Further, with the advent of lower cost sequencing, the amount and complexity of information that is conveyed to patients, including secondary results, has increased. As part of the Clinical Sequencing Ev...

Objective To describe the training and early implementation of the ARIA model of genetic counseling (Accessible, Relational, Inclusive, Actionable). Methods As part of the Cancer Health Assessments Reaching Many (CHARM) study, an interdisciplinary workgroup developed the ARIA curriculum and trained genetic counselors to return exome sequencing res...

Introduction: The Cancer Health Risk Assessments Reaching Many (CHARM) study (NCT03426878) aims to increase access to genetic testing for hereditary cancer in low-income, low-literacy, and minority populations (hereafter referred to as “underserved”). To implement the study, we have capitalized on the availability of electronic medical record (EMR)...

Background Trisomy 13 and trisomy 18 are common life-limiting conditions associated with major disabilities. Many parents have described conflictual relationships with clinicians, but positive and adverse experiences of families with healthcare providers have not been well described. Aim (1) To investigate parental experiences with clinicians and...

Advances in sequencing technologies permit the analysis of a larger selection of genes for preconception carrier screening. The study was designed as a sequential carrier screen using genome sequencing to analyze 728 gene-disorder pairs for carrier and medically actionable conditions in 131 women and their partners (n = 71) who were planning a preg...

Genomic carrier screening can identify more disease-associated variants than existing carrier screening methodologies, but its utility from patients’ perspective is not yet established. A randomized controlled trial for preconception genomic carrier screening provided an opportunity to understand patients’ decisions about whether to accept or decli...

Background: Individual genome sequencing results are valued by patients in ways distinct from clinical utility. Such outcomes have been described as components of "personal utility," a concept that broadly encompasses patient-endorsed benefits, that is operationally defined as non-clinical outcomes. No empirical delineation of these outcomes has b...

Purpose: There is debate within the genetics community about the optimal term to describe genetic variants unrelated to the test indication but potentially important for health. Given the lack of consensus and the importance of adopting terminology that promotes effective clinical communication, we sought the opinion of clinical genetics patients....

Background/aims: In the context of research on medical practices, which includes comparative effectiveness research and pragmatic clinical trials, empirical studies have begun to raise questions about the extent to which institutional review boards' interpretations and applications of research regulations align with patients' values. To better und...

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Huma...

Background: Human subjects protection in healthcare contexts rests on the premise that a principled boundary distinguishes clinical research and clinical practice. However, growing use of evidence-based clinical practices by health systems makes it increasingly difficult to disentangle research from a wide range of clinical activities that are som...

As genome or exome sequencing (hereafter genome-scale sequencing) becomes more integrated into standard care, carrier testing is an important possible application. Carrier testing using genome-scale sequencing can identify a large number of conditions, but choosing which conditions/genes to evaluate as well as which results to disclose can be compl...

There is a recent consensus that more clinical trials are required to assess the safety and efficacy of second-generation antipsychotic medications for children and youth. This shift represents a change in ethical thinking in recent decades. Historically there has been a reluctance to include children and adolescents in medical research due to thei...

Policies have been developed to protect vulnerable populations in clinical research, including the US federal research regulations (45 Code of Federal Regulations 46 Subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or m...

Genomic sequencing is being rapidly introduced into pediatric clinical practice. The results of sequencing are distinctive for their complexity and subsequent challenges of interpretation for generalist and specialist pediatricians, parents, and patients. Pediatricians therefore need to prepare for the professionally responsible disclosure of seque...

We conducted focus groups to assess patient attitudes toward research on medical practices in the context of usual care. We found that patients focus on the implications of this research for their relationship with and trust in their physicians. Patients view research on medical practices as separate from usual care, demanding dissemination of info...

Different types of consent are used to obtain human biospecimens for future research. This variation has resulted in confusion regarding what research is permitted, inadvertent constraints on future research, and research proceeding without consent. The National Institutes of Health (NIH) Clinical Center's Department of Bioethics held a workshop to...

To improve the neurologic outcomes for infants with brain injury, neonatal providers are increasingly implementing neurocritical care approaches into clinical practice. Term infants with brain injury have been principal beneficiaries of neurologically-integrated care models to date, as evidenced by the widespread adoption of therapeutic hypothermia...

In 1995, the American Society of Human Genetics (ASHG) and American College of Medical Genetics and Genomics (ACMG) jointly published a statement on genetic testing in children and adolescents. In the past 20 years, much has changed in the field of genetics, including the development of powerful new technologies, new data from genetic research on c...

As genome sequencing technology advances, research is needed to guide decision-making about what results can or should be offered to patients in different clinical settings. We conducted three focus groups with individuals who had prior preconception genetic testing experience to explore perceived advantages and disadvantages of genome sequencing f...

A commentary on "SUPPORT and the Ethics of Study Implementation: Lessons for Comparative Effectiveness Research from the Trial of Oxygen Therapy for Premature Babies," by John D. Lantos and Chris Feudtner, in the January-February 2015 issue. © 2015 The Hastings Center.

This Viewpoint discusses the importance of effective patient-physician communication when addressing high-stakes medical decisions. Even with full resuscitation efforts, 2 of 3 newborns delivered at 23 weeks’ gestation die. Approximately 90% of survivors have moderate to serious disability.¹ These unpredictable and life-threatening outcomes inform...

The U.S. Office for Human Research Protections has proposed that end points of randomized trials comparing the effectiveness of standard medical practices are risks of research that would require disclosure and written informed consent, but data are lacking on the views of potential participants. To assess attitudes of U.S. adults about risks and p...

Clinical research ethics consultation services have been established across academic health centers over the past decade. This paper presents the results of collaboration within the CTSA consortium to develop a standard approach to the collection of research ethics consultation information to serve as a foundation for quality improvement, education...

The integration of genome scale sequencing into clinical practice for reproductive decision making raises similar policy issues for carrier testing for cystic fibrosis and sickle cell anemia. In all cases, the importance of the information is based on personal values, rather than medical benefit. Policy decisions to fund such testing will depend on...

Background: Evidence shows both a tendency for research participants to conflate research and clinical care and limited public understanding of research. Conflation of research and care by participants is often referred to as the therapeutic misconception. Despite a lack of evidence, few studies have explicitly asked participants, and especially m...

U.S. regulations governing pediatric research do not specify the assent process. To identify best practices, it is important to examine parents' and adolescents' views. The present study focuses on parents' and adolescents' views regarding possible research risks and the influence of financial compensation on their willingness to accept research pr...

Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified pote...

The complexity of biomedical research has increased considerably in the last decade, as has the pace of translational research. This complexity has generated a number of novel ethical issues for clinical investigators, institutional review boards (IRBs), and other oversight committees. In response, many academic medical centers have created formal...

In March 2013, the Office of Human Research Protection (OHRP) issued a finding against the University of Alabama and other institutions for failing to meet regulatory informed consent requirements, in particular regarding reasonably foreseeable risks during the conduct of the Surfactant, Positive Pressure, and Oxygenation Randomized Trial.1 This st...

Introduction: Industry, clinicians, advocacy, and families have a stake in the success of clinical trials (CTs). Understanding decision-makers’ perceptions of CTs inform efforts to improve recruitment; this is particularly relevant for rare diseases like Duchenne/Becker muscular dystrophy (DBMD). Methods: The study team employed a community-based p...

Introduction: Parents’ decisions about enrolling children in Duchenne/Becker muscular dystrophy (DBMD) clinical trials (CTs) may be influenced by hopes and expectations, which when unrealistic may challenge informed consent. We explore influences on decision-making. Methods: The study team employed a community-based participatory research approach....

Purpose Adolescents join clinical research after investigators obtain their positive agreement or “assent.” Although intended to respect adolescents, little is known about the views of adolescents or their parents regarding assent or research enrollment decisions. This study aimed to better understand perspectives of adolescent research participant...

Two cases in which patients have been determined to be dead according to neurologic criteria ("brain death") have recently garnered national headlines. In Oakland, California, Jahi McMath's death was determined by means of multiple independent neurologic examinations, including one ordered by a court. Her family refused to accept that she had died...

Trisomy 13 and trisomy 18 (T13-18) are associated with high rates of perinatal death and with severe disability among survivors. Prenatal diagnosis (PND) may lead many women to terminate their pregnancy but some women choose to continue their pregnancy. We sent 503 invitations to answer a questionnaire to parents who belong to T13 and 18 internet s...

Parental requests for gastrostomies, tracheostomies, or assisted ventilation in children with profound disabilities raise ethical concerns about children's interests, parental decision-making, and health care costs. The underlying concern for many relates to the perceived value of these children. Clinicians should make efforts to appreciate the fam...

There is broad recognition of the need for population-based research to assess the safety and efficacy of newborn screening (NBS) for conditions that are not on current panels. However, prospective population-based research poses significant ethical, regulatory, and logistical challenges. In the context of NBS, there have been a variety of approach...

The Office of Human Research Protections was not justified in issuing findings against the SUPPORT Institutions. Our community can learn from the evolving healthcare transformation into learning health systems by thinking about the novel ethical issues about standard of care research raised by the SUPPORT with the same spirit of quality improvement...

This case explores the ethical landscape around recontacting a subject's relatives to return genetic research results when the informed consent form signed by the original cohort of subjects is silent on whether investigators may share new information with the research subject's family. As a result of rapid advances in genetic technology, methods t...

This case looks at the question of how to consider obligations of confidentiality by a mental health professional who works for an institution and learns that a student has been using a drug intended for an animal research project. Dr. Paul Appelbaum, MD, a psychiatrist at Columbia University, examines the issue of the limits of confidentiality. Ni...

The American College of Medical Genetics and Genomics recently issued recommendations for reporting incidental findings from clinical whole-genome sequencing and whole-exome sequencing. The recommendations call for evaluating a specific set of genes as part of all whole-genome sequencing/whole-exome sequencing and reporting all pathogenic variants...

Whole-genome sequencing (WGS) has advanced to a point where it is beginning to be integrated into pediatric practice. With little consensus on how to maximize the benefits of WGS for children, there is a growing need for focused efforts that connect researchers, clinicians, and families to chart a path forward. To illustrate relevant concerns, two...

Health behaviors such as tobacco use contribute significantly to poor health. It is widely recognized that efforts to prevent poor health outcomes should begin in early childhood. Biomedical enhancements, such as a nicotine vaccine, are now emerging and have potential to be used for primary prevention of common diseases. In anticipation of such enh...

To the Editor: We are a group of scholars and leaders in bioethics and pediatrics with extensive experience in ethical and regulatory issues in pediatrics and human subjects research. We urge the Office for Human Research Protections (OHRP) to withdraw its notification to the institutions involved in the Surfactant, Positive Pressure, and Oxygenati...

Emphasis on translational research to facilitate progression from the laboratory into the community also creates a dynamic in which ethics and social policy questions and solutions are ever pressing. In response, academic institutions are creating Research Ethics Consultation Services (RECS). All Clinical Translational Science Award institutions we...

This paper is a case study of our regional Clinical Translational Science Award's (CTSA) development of a coordinated response to the advanced notice of proposed rulemaking on Human Subjects Research Protections during the fall of 2011. Our CTSA was well positioned to quickly activate and coordinate a response to this important and time sensitive i...

Children with trisomy 13 and trisomy 18 (T13-18) have low survival rates and survivors have significant disabilities. For these reasons, interventions are generally not recommended by providers. After a diagnosis, parents may turn to support groups for additional information. We surveyed parents of children with T13-18 who belong to support groups...

In this issue, Greer Donley, Sara Chandros Hull, and Benjamin E. Berkman explore the implications of using whole genome sequencing in the prenatal context. They focus on how whole genome sequencing may refine pregnancy expectations, impact child-rearing decisions, and foreclose children's desire not to know more about their future. Their paper insp...

Recruiting research participants based on genetic information generated about them in a prior study is a potentially powerful way to study the functional significance of human genetic variation. However, it also presents significant ethical challenges that, to date, have received only minimal consideration. We convened a multi-disciplinary workshop...

Biobanks and archived data sets collecting samples and data have become crucial engines of genetic and genomic research. Unresolved, however, is what responsibilities biobanks should shoulder to manage incidental findings and individual research results of potential health, reproductive, or personal importance to individual contributors (using “bio...

This article considers how to approach assent from children for genomics research. We examine the “protection” rationale for assent, which emerged in the context of a historical debate regarding whether it was ever acceptable to subject children to risks of research for the benefit of others. We also consider the “development” rationale for assent,...

Genotype-driven recruitment is a potentially powerful approach for studying human genetic variation but presents ethical challenges. We conducted in-depth interviews with research participants in six studies where such recruitment occurred. Nearly all responded favorably to the acceptability of recontact for research recruitment, and genotype-drive...

As genetic research is increasingly conducted in children, it is important to understand how parents make decisions about enrolling their children and what they think about receiving their children's genetic research results. We conducted semi-structured phone interviews with 23 parents of children enrolled in genetic studies of autism or diabetes....

Purpose: Improvements in cancer outcomes for adolescents and young adults with cancer lag behind those of other age groups, and few psychosocial interventions have been developed specifically for this population. This study sought to explore both adolescent cancer patients' interest in engaging in a participatory study and their perceived coping ne...

Genetic testing offered by direct-to-consumer companies-herein referred to as "predictive genomic testing"--has come under federal scrutiny. Critics claim testing yields uninterpretable and potentially harmful information. Supporters assert individuals have a right to this information, which could catalyze preventive health actions. Despite content...

The psychological consequences of carrier screening for genetic conditions can include impacts on self‐efficacy, self‐concept, anxiety and understanding. Studies suggest that individuals’ willingness to undergo screening and their psychological responses to screening are variable, influenced by factors relating to programme design, presentation of...

To describe parents' attitudes toward pediatric genetic testing for common, adult-onset health conditions and to identify factors underlying these attitudes. Parents (n = 219) enrolled in a large, group-practice health plan were offered a "multiplex" genetic test for susceptibility to 8 common, adult-onset health conditions and completed an online...

Bookman et al. write to correct the impression given in the Commentary by Kohane and Taylor that the recommendations of the National Heart, Lung, and Blood Institute (NHLBI) Working Group "Reporting Genetic Results in Research Studies" included advice to return genetic information to research subjects only in cases where there is a proven or preven...

This paper describes an ongoing randomized controlled trial designed to assess the impact of genetic and environmental risk assessment (GERA) on colorectal cancer (CRC) screening. The trial includes asymptomatic patients who are 50-79years and are not up-to-date with CRC screening guidelines. Patients who responded to a baseline telephone survey ar...

These five letters to the editor focus on three themes: the lack of evidence of benefit, the potential for distraction from addressing the broader social issues facing people with disabilities, and the problem of singling out children with profound cognitive disabilities. Armand Antommaria notes that the working group’s justification for growth att...

A twenty-person working group convened to discuss the ethical and policy considerations of the controversial intervention called “growth attenuation,” and if possible to develop practical guidance for health professionals. A consensus proved elusive, but most of the members did reach a compromise.

Leftover newborn spots can provide a powerful research tool as a population-wide DNA bank. Some provinces/states store them for more than 20 years; however, parents are usually not informed of the retention of leftover newborn spots. To examine the opinions of Canadian geneticists regarding permission for leftover newborn spots storage for research...

It is unclear how the possible effects of genetic research on socially identifiable groups may impact patient willingness to donate biological samples for future genetic studies. Telephone interviews with patients at 5 academic medical centers in the U.S. examined how patients' beliefs about benefits and harms to ones racial or ethnic group shape d...

As advances in research have made a growing number of genetic tests available, clinicians will increasingly be faced with making decisions about when offering genetic testing services to children is appropriate. A key factor in such decisions involves determining whether knowledge of genetic health risks might have an impact on children's psychosoc...

One possible method of integrating genomic information into public health practice is to offer susceptibility testing for health related-conditions as part of standard prenatal, newborn, or pediatric care. This approach may be especially beneficial for primary prevention because many risk factors for common health conditions arise in early life. Ho...

The traditional approach to resolving ethics concerns may not address underlying organisational issues involved in the evolution of these concerns. This represents a missed opportunity to improve quality of care "upstream". The purpose of this study was to understand better which organisational issues may contribute to ethics concerns. Directed con...

Proposals for pediatric biobanks have prompted questions of whether parental permission is sufficient to continue to use biological samples and data after the children become adults. The objective of this study was to examine adults' attitudes about continued research with their pediatric samples/data, particularly when they could not be located to...

Ethical evaluation of genetic testing in children is traditionally based on balancing clinical benefits and risks. However, this focus can be inconsistent with the general practice of respecting parental decision-making about their children's health care. We argue that respect for parental decision-making should play a larger role in shaping pediat...